Association of variants at UMOD with chronic kidney disease and kidney stones-role of age and comorbid diseases

PLoS Genet. 2010 Jul 29;6(7):e1001039. doi: 10.1371/journal.pgen.1001039.


Chronic kidney disease (CKD) is a worldwide public health problem that is associated with substantial morbidity and mortality. To search for sequence variants that associate with CKD, we conducted a genome-wide association study (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We observed an association between CKD and a variant with 80% population frequency, rs4293393-T, positioned next to the UMOD gene (GeneID: 7369) on chromosome 16p12 (OR = 1.25, P = 4.1x10(-10)). This gene encodes uromodulin (Tamm-Horsfall protein), the most abundant protein in mammalian urine. The variant also associates significantly with serum creatinine concentration (SCr) in Icelandic subjects (N = 24,635, P = 1.3 x 10(-23)) but not in a smaller set of healthy Dutch controls (N = 1,819, P = 0.39). Our findings validate the association between the UMOD variant and both CKD and SCr recently discovered in a large GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases substantially with both age (P = 3.0 x 10(-17)) and number of comorbid diseases (P = 0.008). The association with CKD is also stronger in the older age groups. These results suggest that the UMOD variant may influence the adaptation of the kidney to age-related risk factors of kidney disease such as hypertension and diabetes. The variant also associates with serum urea (P = 1.0 x 10(-6)), uric acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7 x 10(-5)).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Case-Control Studies
  • Comorbidity
  • Creatinine / blood
  • Genetic Variation*
  • Genome-Wide Association Study*
  • Gout
  • Humans
  • Iceland
  • Kidney Calculi / genetics*
  • Netherlands
  • Polymorphism, Single Nucleotide
  • Renal Insufficiency, Chronic / genetics*
  • Risk Factors
  • Urea / blood
  • Uric Acid / blood
  • Uromodulin / genetics*


  • UMOD protein, human
  • Uromodulin
  • Uric Acid
  • Urea
  • Creatinine